Apparatus and method for the automated measurement of sural nerve conduction velocity and amplitude

ABSTRACT

Apparatus for measuring sural nerve conduction velocity and amplitude, the apparatus including a housing; stimulation means for electrically stimulating a human sural nerve; a biosensor comprising a plurality of electrodes for detecting a sural nerve response evoked by the stimulation means; acquisition means electrically connected to the biosensor for electrically acquiring the sural nerve response detected by the biosensor; processing means electrically connected to the acquisition means for digitizing, processing and storing the acquired sural nerve response; calculation means electrically connected to the processing means for calculating the conduction velocity and amplitude of the processed sural nerve response; and display means for displaying the sural nerve conduction velocity and amplitude; wherein the stimulation means and the biosensor are designed to be placed on a patient&#39;s anatomy, in the vicinity of a sural nerve.

REFERENCE TO PENDING PRIOR PATENT APPLICATIONS

This patent application claims benefit of:

-   -   (i) prior U.S. Provisional Patent Application Ser. No.        61/403,453, filed Sep. 16, 2010 by Shai N. Gozani for NC-STAT®        SL;    -   (ii) prior U.S. Provisional Patent Application Ser. No.        61/459,127, filed Dec. 6, 2010 by Shai N. Gozani for NC-STAT®        SL;    -   (iii) prior U.S. Provisional Patent Application Ser. No.        61/467,857, filed Mar. 25, 2011 by Shai N. Gozani et al. for        NC-STAT® SL;    -   (iv) prior U.S. Provisional Patent Application Ser. No.        61/516,944, filed Apr. 11, 2011 by Bonniejean Boettcher et al.        for NC-STAT® SL; and    -   (v) prior U.S. Provisional Patent Application Ser. No.        61/571,203, filed Jun. 22, 2011 by Shai N. Gozani et al. for        NC-STAT® DPNCHECK™.

The five (5) above-identified patent applications are herebyincorporated herein by reference.

FIELD OF THE INVENTION

This invention relates to apparatus and methods for the assessment ofelectrophysiological signals, and more particularly to the assessment ofsural nerve conduction velocity and amplitude.

BACKGROUND OF THE INVENTION

Diabetes Mellitus (“DM”) is a common disease involving ineffectiveregulation of blood glucose levels. There are over 25 million people inthe United States with DM, and recent projections suggest that over 350million people have the disease worldwide. There are two primary formsof DM. Type I DM generally affects children and young adults and isrelated to a primary deficiency of the insulin hormone. Type II DMusually affects adults, often over the age of 50, but increasingly inyounger adults as well. It is a complex disease that generally starts asa resistance to insulin action that may progress to secondary insulindeficiency. The causes of Type I and Type II DM are not entirely knownalthough genetic, environmental, and lifestyle risk factors have beenidentified.

Although acutely high or low blood glucose levels are dangerous, theprimary sources of DM-associated morbidity and mortality are the longterm macrovascular and microvascular complications of the disease.Macrovascular complications refer to cardiovascular events such asmyocardial infarction (“heart attack”) and stroke. Microvascularcomplications refer to pathological damage to the nerves, eyes, andkidneys of people with DM.

The most common microvascular complication of DM is neuropathy, or nervedamage. Diabetic neuropathy affects 60% or more of people with DM.Diabetic neuropathy may include damage to the large myelinated nervefibers, the small myelinated and unmyelinated nerve fibers, and theautonomic nerves. The most common form of diabetic neuropathy is thelarge fiber form of the disease which is often termed diabeticperipheral neuropathy (“DPN”). DPN leads to pain and disability, and isthe primary trigger for foot ulcers which may result in lower extremityamputations.

Because of the severe consequences of DPN, early detection of thiscomplication of DM, and interventions to prevent or slow downprogression of the neuropathy, are of paramount importance.Unfortunately, detection of DPN is challenging, particularly at itsearly stages when it may be most susceptible to intervention. Currentmethods of detecting and monitoring DPN range from clinical evaluation(including symptoms and signs obtained on simple physical examination)to various tests that include the 5.07/10-g monofilament test (where acolumn of “fishing line” is pressed into the foot of the patient, withthe goal being for the patient to detect the contact before the columnof “fishing line” bends), the tuning fork test (where a vibrating tuningfork is placed against the big toe of the patient, with the goal beingfor the patient to detect the vibration of the tuning fork), andquantitative vibration perception testing (where electronics are used tomeasure the magnitude of a vibration detectable by the patient). Whileall of these methods have utility, they are subjective, have inadequatesensitivity or specificity, or both, and have poor reproducibility. The“gold standard” method for evaluation of DPN is a nerve conductionstudy. In a nerve conduction study, a nerve is electrically stimulatedat a first location along the nerve, and then the electrical response ofthe nerve is detected at a second location along the nerve. Among otherthings, the rate at which the nerve conducts the signal (“the nerveconduction velocity”) and the magnitude of the evoked signal (“theamplitude”) are reliable indicators of neuropathy. Unlike theaforementioned techniques, nerve conduction testing is objective,sensitive, specific, and reproducible. As a result, most clinicalguidelines suggest confirmation of DPN by nerve conduction testing for areliable diagnosis.

Despite its technical and clinical attributes, nerve conduction testingis not currently widely used in the detection and monitoring of DPN. Thereasons for this include the limited availability, complexity and highcost of the study when performed by specialists, usually a neurologist,using traditional electrodiagnostic equipment. To overcome theseobstacles to adoption, a number of devices have been developed tosimplify and increase access to nerve conduction studies throughautomation and other techniques. For example, devices that perform nerveconduction measurements using pre-fabricated, nerve-specific electrodearrays have been developed that largely automate the required technicalsteps of a nerve conduction study (see, for example, U.S. Pat. No.5,851,191 issued to Gozani et al. and U.S. Pat. No. 7,917,201 issued toGozani et al.). Another related solution found in the prior art (seeU.S. Pat. No. 5,215,100 issued to Spitz et al.) is an apparatus for theassessment of Carpal Tunnel Syndrome (CTS) in which all the electrodesrequired to stimulate and record from the nerve are fixed by the device.

These prior art solutions suffer from a number of deficiencies. Alldevices described in the prior art are either general purpose (i.e.,multi-nerve, multi-application) nerve conduction testing devices or theyare designed specifically for evaluation of the median nerve for theassessment of CTS. General purpose devices, of necessity, must adapt tothe various anatomical and electrophysiological aspects of manydifferent nerves. As a result, only limited customization is possibleand the onus remains on the user of the general purpose device toaddress the sources of variations—such as through the placement ofindividual electrodes or even pre-configured electrode arrays. As aresult, despite simplifying nerve conduction measurements relative tothe traditional approaches, the general purpose testing devices stillrequire a fair amount of training in order to properly perform the nerveconduction test procedures. Also, those devices in the prior artspecifically designed for the evaluation of the median nerve have littlerelevance to the requirements of the present invention, which is theassessment of the sural nerve. The primary reason for this is that theanatomy and electrophysiology of the sural nerve (used for theassessment of DPN) is substantially different from that of the mediannerve (used for the assessment of CTS). Therefore devices specificallydesigned for testing of the median nerve cannot be used to test thesural nerve. Another issue with general purpose testing devices is thatthey require two discrete components—a device with the electroniccircuits needed to perform a nerve conduction test, and a nerve-specificelectrode array which provides an interface between the uniquecharacteristics of the particular nerve being tested and the commontesting device. This two-component requirement limits attempts to reducetest costs, particularly because it restricts the ability to reduce thesize of the electrode array, which is a primary cost driver in nerveconduction testing.

SUMMARY OF THE INVENTION

The present invention is a fully-integrated, hand-held sural nerveconduction testing device. The sural nerve is a sensory-only nervelocated in the lower calf and ankle region of the body. Sural nerveconduction is a standard and quantitative biomarker of DPN. Sural nerveconduction testing detects DPN with high diagnostic sensitivity andreveals abnormalities before there is clinical evidence of neuropathy.Sural nerve conduction is correlated to the morphological severity ofmyelinated fiber loss and is therefore predictive of foot ulcer risk.

The purpose of this new device is to easily, rapidly, and accuratelymeasure and report two common sural nerve conduction parameters: theonset conduction velocity (hereafter abbreviated as “CV”) and thesensory response amplitude (hereafter described as “amplitude”). Theterm “fully-integrated” indicates that all of the components needed forperforming a nerve conduction test of the sural nerve are incorporatedinto a single physical unit, as opposed two or more distinct components(for example, an electrode array and a testing instrument connected by acable). The term “hand-held” indicates that the device is applied to thepatient by a qualified user in order to test the nerve, rather thanbeing a fixed apparatus into which the patient places their limb. The“fully-integrated” and “hand-held” characteristics require technologicaladvances that are both novel and non-obvious.

The present invention addresses the deficiencies of the prior art.First, the current device is designed and optimized for testing of thesural nerve. As a result, the test procedure has been substantiallysimplified and automated to the point where it can be taught to someonein 30-60 minutes after which they should be able to obtain accuratesural nerve conduction results. Further, due to its focused applicationon the sural nerve, the test procedure has been automated to the pointwhere the test duration is typically only 15-30 seconds in length.Another benefit of its focused application on the sural nerve is thatthe cost of both the hardware and disposable components have beensubstantially reduced relative to the general purpose devices describedin the prior art.

In one preferred form of the present invention, there is providedapparatus for measuring sural nerve conduction velocity and amplitude,the apparatus comprising:

-   -   a housing;    -   stimulation means mounted to the housing for electrically        stimulating a human sural nerve;    -   a biosensor releasably mounted to the housing, the biosensor        comprising a plurality of electrodes for detecting a sural nerve        response evoked by the stimulation means;    -   acquisition means mounted to the housing and electrically        connected to the biosensor for electrically acquiring the sural        nerve response detected by the biosensor;    -   processing means mounted to the housing and electrically        connected to the acquisition means for digitizing, processing        and storing the acquired sural nerve response;    -   calculation means mounted to the housing and electrically        connected to the processing means for calculating the conduction        velocity and amplitude of the processed sural nerve response;        and    -   display means mounted to the housing for displaying the sural        nerve conduction velocity and amplitude;    -   wherein the stimulation means and the biosensor are designed to        be placed on a patient's anatomy, in the vicinity of a sural        nerve, by manipulating the housing.

In another preferred form of the present invention, there is providedapparatus for measuring sural nerve conduction velocity and amplitude,the apparatus comprising:

-   -   a housing;    -   stimulation means mounted to the housing for electrically        stimulating a human sural nerve;    -   a seat on the housing for releasably mounting a biosensor to the        housing, wherein the biosensor is of the type comprising a        plurality of electrodes for detecting a sural nerve response        evoked by the stimulation means;    -   acquisition means mounted to the housing for electrical        connection to a biosensor mounted on the seat and for        electrically acquiring the sural nerve response detected by the        biosensor;    -   processing means mounted to the housing and electrically        connected to the acquisition means for digitizing, processing        and storing the acquired sural nerve response;    -   calculation means mounted to the housing and electrically        connected to the processing means for calculating the conduction        velocity and amplitude of the processed sural nerve response;        and    -   display means mounted to the housing for displaying the sural        nerve conduction velocity and amplitude;    -   wherein the stimulation means and a biosensor releasably mounted        on the seat are designed to be placed on a patient's anatomy, in        the vicinity of a sural nerve, by manipulating the housing.

In another preferred form of the present invention, there is providedapparatus for measuring sural nerve conduction velocity and amplitude,the apparatus comprising:

-   -   a biosensor adapted to be releasably mounted to the housing of a        nerve conduction testing device so that the biosensor moves in        conjunction with the housing, the biosensor comprising a        plurality of electrodes for detecting a sural nerve response        evoked by the nerve conduction testing device and an electrical        connector for electrically connecting the plurality of        electrodes to the nerve conduction testing device.

In another preferred form of the present invention, there is provided amethod for measuring sural nerve conduction velocity and amplitude, themethod comprising:

-   -   releasably mounting a biosensor to the housing of a nerve        conduction testing device so that the biosensor moves in        conjunction with the housing;    -   positioning the housing of the nerve conduction testing device        so that the nerve conduction testing device is positioned to        electrically stimulate a human sural nerve and the biosensor is        positioned to detect a sural nerve response evoked by the        stimulation means;    -   using the nerve conduction testing device to electrically        stimulate a sural nerve and to acquire the sural nerve response        detected by the biosensor; and    -   processing the acquired sural nerve response to determine the        conduction velocity and amplitude of the processed sural nerve        response.

In another preferred form of the present invention, there is provided afully-integrated, hand-held nerve conduction testing apparatuscomprising a hand-held component and a single-patient use biosensor,wherein the biosensor is both physically and electrically connected tothe hand-held component to acquire a nerve response.

In another preferred form of the present invention, there is provided abiosensor for detecting a nerve response, the biosensor comprising:

-   -   a substrate;    -   a plurality of electrodes mounted to the substrate for detecting        the nerve response; and    -   a biosensor reuse code carried by the substrate for determining        reuse of the biosensor, wherein the biosensor reuse code is        randomly assigned to that biosensor.

In another preferred form of the present invention, there is provided akit comprising:

-   -   a plurality of biosensors for detecting nerve responses, wherein        each of the biosensors comprises a substrate, a plurality of        electrodes mounted to the substrate for detecting a nerve        response, and a biosensor reuse code carried by the substrate        for determining reuse of the biosensor;    -   wherein the biosensor reuse code varies randomly among the        biosensors in the kit.

In another preferred form of the present invention, there is provided amethod for determining the reuse of a biosensor in connection with atest machine, the method comprising the steps of:

-   -   connecting a biosensor to the test machine, wherein the        biosensor comprises a biosensor reuse code randomly assigned to        that biosensor;    -   identifying the biosensor reuse code associated with the        connected biosensor;    -   comparing the identified biosensor reuse code with the biosensor        reuse codes associated with the biosensors previously connected        to the test machine; and    -   determining that the biosensor has been reused if the comparison        indicates that the identified biosensor reuse code and the codes        from the previously connected biosensors form a pattern that is        unlikely from a random distribution of biosensor reuse codes, or        determining that the biosensor has not been reused if the        aforementioned pattern is likely from a random distribution of        biosensor reuse codes.

In another preferred form of the present invention, there is provided amethod for preventing the reuse of a biosensor in connection with a testmachine, the method comprising the steps of:

-   -   connecting a biosensor to the test machine, wherein the        biosensor comprises a biosensor reuse code randomly assigned to        that biosensor;    -   identifying the biosensor reuse code associated with the        connected biosensor;    -   comparing the identified biosensor reuse code with the biosensor        reuse codes associated with the biosensors previously connected        to the test machine; and    -   allowing the test to proceed if the comparison indicates that        the identified biosensor reuse code is part of a random        distribution of biosensor reuse codes, or preventing the test        from proceeding if the comparison indicates that the identified        biosensor reuse code is not part of a random distribution of        biosensor reuse codes.

In another preferred form of the present invention, there is provided anadapter for connecting a biosensor to a testing device, the adaptercomprising a biosensor reuse code carried by the adapter for determiningreuse of the biosensor, wherein the biosensor reuse code is presented bythe adapter to the testing device.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other objects and features of the present invention will bemore fully disclosed or rendered obvious by the following detaileddescription of the preferred embodiments of the invention, which is tobe considered together with the accompanying drawings wherein likenumbers refer to like parts, and further wherein:

FIG. 1 is a schematic view of a novel, fully-integrated, hand-held suralnerve conduction testing device formed in accordance with the presentinvention;

FIG. 2 is a schematic view showing the testing device of FIG. 1 beingplaced on a patient's limb;

FIG. 3 is a schematic view of the bottom of the testing device shown inFIG. 1;

FIGS. 3A and 3B are schematic sectional views showing the preferredconstruction details for the spring-loaded cathode of the testing deviceshown in FIG. 1;

FIG. 4 is a schematic view showing selected portions of the testingdevice of FIG. 1, including the biosensor, foam pad, and device head;

FIG. 5 is a schematic view of the top of the testing device shown inFIG. 1;

FIG. 6 is a schematic view of the top of the biosensor;

FIG. 6A is a schematic side view of the biosensor shown in FIG. 6;

FIG. 6B is a schematic end view of the biosensor shown in FIG. 6;

FIG. 7 is another schematic view of the top of the biosensor shown inFIG. 6;

FIG. 7A is a schematic cross-sectional view taken along line 7A-7A ofFIG. 6;

FIG. 7B is a schematic cross-sectional view taken along line 7B-7B ofFIG. 6;

FIG. 7C is an enlarged schematic view of selected portions of the tracesof the biosensor shown in FIG. 6;

FIG. 8 is a high level hardware schematic of the testing device shown inFIG. 1;

FIG. 9 is a schematic view showing sural nerve responses from tworecording channels;

FIG. 10 is an example of an algorithmic analysis of a sural nerveresponse;

FIG. 11 is an example of how to determine sural nerve response waveformfeatures; and

FIG. 12 is a high level functional schematic of the preferred controlalgorithm for the testing device of FIG. 1.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Device Description

The present invention is a fully-integrated, hand-held sural nerveconduction testing device. The device is designed exclusively fornon-invasive nerve conduction measurements of the human sural nerve inthe region of the lower calf and ankle. The sural nerve is analmost-entirely sensory nerve formed from the merger of the medial andlateral sural cutaneous nerves which are branches of the tibial andcommon fibular nerves (which are themselves branches of the sciaticnerve). After forming at the distal third of the gastroc muscle, thesural nerve runs down the leg on the posterior-lateral side, thenposterior to the lateral malleolus where it runs deep to the fibularistendon sheath and reaches the lateral tuberosity of the fifth toe, whereit ramifies. The sural nerve transmits sensory signals from theposterior lateral corner of the leg, the lateral foot and the 5th toe.

Sural nerve conduction is a standard and quantitative biomarker of DPN.Sural nerve conduction testing detects DPN with high diagnosticsensitivity and reveals abnormalities before there is clinical evidenceof neuropathy. Sural nerve conduction is correlated to the morphologicalseverity of myelinated fiber loss and is therefore predictive of footulcer risk.

There are a variety of nerve conduction methodologies by which the suralnerve can be evaluated. For example, the nerve can be testedorthodromically by stimulating the nerve at the ankle and then measuringthe nerve response after it has conducted a known distance up the calf,or the nerve can be tested antidromically by stimulating the nerve inthe calf and then measuring the nerve response after it has conducted aknown distance to the ankle. Another methodological factor in nerveconduction testing for the sural nerve includes the distance between thepoints of stimulation and recording, which generally varies from about 8cm to 16 cm. Another methodological factor associated with nerveconduction testing of the sural nerve is the configuration of therecording electrodes, including their shape, size, and the distancebetween them. In the preferred embodiment of the present invention, thesural nerve is tested orthodromically with a stimulation-to-recordingdistance of 9.22 cm. The preferred recording electrode configuration isprovided below in the description of the biosensor.

The purpose of the present invention is to easily, rapidly, andaccurately measure and report two common sural nerve conductionparameters: the onset conduction velocity (hereafter abbreviated as“CV”) and the sensory response amplitude (hereafter described as“amplitude”). The term “fully-integrated” indicates that all of thecomponents needed for performing a nerve conduction test of the suralnerve are incorporated into a single physical unit, as opposed two ormore distinct components (for example, an electrode array and a testinginstrument connected by a cable). The term “hand-held” indicates thatthe device is applied to the patient by a qualified user in order totest the nerve, rather than being a fixed apparatus into which thepatient places their limb. The “fully-integrated” and “hand-held”characteristics require technological advances that are both novel andnon-obvious.

An overall view of the present invention is provided in FIG. 1. Asshown, the invention comprises a single fully-integrated, hand-helddevice 1 with a narrow handle 2 and a head 3. In the preferredembodiment, device 1 is 19.0 cm in length and 11.5 cm in width at itswidest point on head 3. The most critical dimension is the distancebetween cathode 10 (FIG. 3) of device 1 (which is the point of nervestimulation) and the center of the electrodes 41, 43 on the biosensor30. When biosensor 30 is seated in the biosensor port 16 (FIG. 3),electrodes 41, 43 are closest to cathode 10. That distance (i.e., thedistance between cathode 10 and electrodes 41, 43) represents theconduction distance between the point of nerve stimulation via cathode10 and arrival of the evoked nerve impulse at electrodes 41, 43. Thisdistance is 9.22 cm in the preferred construction and is used tocalculate the CV as will be described below.

A preferred use of the invention is shown in FIG. 2. As shown, device 1is placed against the lateral aspect of the patient's lower leg 5 suchthat (i) the stimulation probes 10, 11 (FIG. 3) mechanically contact theleg immediately behind the outside ankle bone (“lateral malleoulus”) 6,and (ii) biosensor 30 contacts the patient's lower calf 7, with theinner edge (one of the two sides 8 or 9, depending on the limb) ofdevice 1 being approximately aligned with the Achilles tendon. In orderto reliably measure nerve conduction of the sural nerve, device 1 musthave enough degrees of freedom in order to conform to the patient'slower leg anatomy and thereby allow for robust and stable contact ofcertain device components (i.e., the stimulating electrodes and thedetecting electrodes) with the patient. The means to accomplish thisrobust electrical contact are described in detail below.

FIG. 3 is a bottom view of the preferred embodiment of device 1. Thisview shows the surfaces that contact the patient. There are twostainless steel probes 10, 11 for electrically stimulating the suralnerve when device 1 is placed against the patient in the manner shown inFIG. 2. The cathode 10 has a variable height relative to handle 2 due toits spring-loaded construction. In the preferred embodiment thisvariable height ranges from 2.5 cm (compressed condition) to 3.3 cm(uncompressed condition) from handle 2. The anode 11 preferably has afixed height relative to handle 2, which in the preferred embodiment isfixed at 2.3 cm from the handle. The variable length cathode 10 is novelinasmuch as it provides a degree of freedom to enable robust contact ofboth stimulating probes 10, 11 with the patient anatomy in the vicinityof the ankle, which is non-planar and has a topology which varies frompatient to patient. Although it is possible to electrically stimulatethe sural nerve through the stimulating probes 10, 11 by direct contactwith the patient's skin, it is preferable to use a small amount ofconductive hydrogel on the outer tip of each probe so as to reduce theimpedance of the probe-skin interface.

FIGS. 3A and 3B show one preferred construction for the spring-loadedcathode 10. More particularly, in this form of the invention, device 1comprises a plastic enclosure 300 which forms the body of device 1, withplastic enclosure 300 comprising a tubular projection 305 for slidablyreceiving cathode 10 therein. A spring 310 is captured between theproximal end of cathode 10 and a seat 315 formed on plastic enclosure300. A fastener 320 may be used to secure spring 310 to the proximal endof cathode 10 if desired. A flexible cable 325 electrically connectscathode 10 to the stimulation source. Also shown in FIGS. 3A and 3B isthe fixed anode 11.

Device 1 includes an infra-red thermometer 14 (FIG. 3) for non-contactmeasurement of the patient's skin surface temperature in the vicinity ofthe ankle bone. As will be discussed below, this temperature measurementis used to compensate for the effects of temperature on nerve conductionresults. The use of a non-contact temperature measuring device is animportant aspect of the present invention, since it permits reliabletemperature measurements to be made in the irregular skin surfacetopology associated with the sural nerve.

Head 3 of device 1 supports biosensor 30, which provides a bioelectricalinterface to the patient. Biosensor 30, which is described in detailbelow, is disposable and should be replaced between patients. Biosensor30 is secured to device 1 by a foam pad 31 (FIGS. 3 and 4) which isprovided with non-permanent adhesive on both sides of the foam pad—theadhesive on the inner surface of foam pad 31 releasably secures the foampad to head 3 of device 1, and the adhesive on the outer surface of foampad 31 releasably secures biosensor 30 to the foam pad. Foam pad 31 isdisposable but may be used for multiple patients as it does not come indirect contact with the patient. Foam pad 31 is shown in greater detailin FIG. 4. One side 32 of the foam pad attaches to the bottom surface ofhead 3 of device 1, and the other side 33 attaches to the non-patientcontact side of biosensor 30. In the preferred embodiment, foam pad 31is 2.2 cm thick. Although various types of foam may be used, in thepreferred embodiment, polyurethane foam is used. When device 1 ispressed against the patient's leg as shown in FIG. 2, the foam padprovides multiple degrees of freedom by which biosensor 30 may conformto the patient's anatomy so as to establish complete contact with thepatient's skin. A uniform and complete contact between electrodes 41,42, 43, 44 and 45 (FIG. 3) and patient skin makes it possible to acquirehigh quality nerve conduction signals over a wide variety of patientanatomy. The use of foam pad 31 in achieving a uniform and completecontact of electrodes and patient skin is novel and non-obvious.Biosensor 30 is connected to the internal electronics of device 1 viabiosensor port 16.

Thus it will be seen that device 1 includes (i) novel means for ensuringreliable electrical contact between the stimulating electrodes and theskin of the patient (i.e., the spring-loaded cathode 10 and thefixed-position anode 11), and (ii) novel means for ensuring reliableelectrical contact between the detecting electrodes and the skin of thepatient (i.e., the use of foam pad 31 to support biosensor 30).

Head 3 of device 1 includes a battery compartment 18 (FIG. 3) with aremovable door for replacement of the battery 109 (FIG. 8), which in thepreferred embodiment is a widely available 3V Lithium Ion battery(CR123A). A mini USB port 20 (FIG. 3) allows for device 1 to communicatewith external devices (such as a PC) using the standard USB protocol.

FIG. 5 shows the top of device 1, which provides the user interface. Inthe preferred embodiment, the user interface consists of one push-buttonswitch 22, an LED 24, and an LCD 26. Push-button switch 22 turns ondevice 1 if the device is powered off. If device 1 is powered on, thenswitch 22 initiates a nerve conduction test. LED 24 has three colors(green, amber, and red) and is used to indicate device status, which mayinclude green to represent “ready to test,” amber to indicate “batterylow,” and red to indicate “error—cannot perform test.” In the preferredembodiment, LCD 26 is a two 7-segment display with additional dotindicators. LCD 26 displays the results of the sural nerve conductiontest or an error status 180 (see FIG. 12) to the user. A successful testis accompanied by a toggling display on the LCD of (i) the numericalvalues of the CV, and (ii) the amplitude of the nerve response (or anamplitude of 0, without a CV, to indicate that sural nerve conduction isnot detectable). An unsuccessful test is accompanied by an error statusmessage 180 (see FIG. 12) on LCD 26 which indicates the probable causefor the failure. In the preferred embodiment, the error status messagesinclude “Sn” for an error related to the biosensor, “Er” for an errorrelated to excessive muscle interference, “Pr” for an error related tostimulating probes, and “° C.” for an error related to patient skinsurface temperature.

Biosensor Description

A preferred embodiment of biosensor 30 is shown in FIGS. 6, 6A, 6B, 7,7A and 7B. Biosensor 30 is a multi-layer construct of mylar 46, Ag(silver) traces 51, Ag—AgCl pads 52, foam 47, and hydrogels 48.Biosensor 30 also comprises a patient contact area 35 and a deviceconnection tail 34 (FIG. 6). Patient contact area 35 preferably has awidth 8.77 cm and a height 3.77 cm. Tail 34 electrically connectsbiosensor 30 to device 1 via biosensor port 16. Biosensor 30 consists of5 discrete electrodes 41, 42, 43, 44, 45 that are comprised of hydrogellayered on top of an Ag—AgCl pad. The four smaller electrodes (41, 42,43 and 44) are electrically connected to the differential inputs ofinstrumentation amplifiers (see below) and therefore function as“active” electrodes. The single long electrode 45 is connected to thereference input of the instrumentation amplifiers and thereforefunctions as a “reference” electrode. In the preferred embodiment ofbiosensor 30, the electrodes are connected so as to form two distinctsural nerve response recording channels. In particular, electrodes 41and 42 comprise one recording channel, and electrodes 43 and 44 comprisea second distinct recording channel. Alternative embodiments of thepresent invention include biosensors comprised of only one recordingchannel, or biosensors comprised of three or more recording channels.Alternative configurations of reference electrode 45 include multipledistinct reference electrodes rather than a single common referenceelectrode.

In the preferred embodiment shown in FIG. 6, the active recordingelectrodes 41, 42, 43 and 44 each have dimensions of 2.5 cm by 0.5 cm,and the reference electrode 45 has dimensions 0.5 cm by 7.0 cm. The twoactive electrodes comprising each recording channel (i.e., 41, 42 and43, 44) are preferably separated by a distance of 2.0 cm measured centerto center. The reference electrode 45 is preferably separated by 1.0 cmfrom each of the active electrodes 41, 42, 43, 44 measured center tocenter.

Tail 34 of biosensor 30 provides an electrical connection between device1 and biosensor 30 via biosensor port 16. Tail 34 is the male connector,and biosensor port 16 is the female connector. In the preferred form ofthe invention, tail 34 comprises 8 parallel traces 51. Five of thetraces (51A, 51B, 51C, 51D and 51E) connect electrodes 41, 42, 43, 44,45, respectively, to the corresponding inputs on the aforementionedinstrumentation amplifiers. Two of the traces (51F and 51G) areconnected together such that when tail 34 of biosensor 30 is insertedinto biosensor port 16 of device 1, an electrical circuit is closed.This closed circuit allows device 1 to detect and thereby confirm thatbiosensor 30 is connected to device 1. Confirmation is indicated to theuser by a steady green color on LED 24. One trace (51H) represents a1-bit biosensor code which is used by the device software to determinewhether biosensors 30 are being reused on multiple patients. The bit iscoded as 0 or 1, depending on whether that trace (51H) is connected(e.g., via a connector 53, see FIG. 7C) to one of the other traces (51F,51G), which is connected to ground upon insertion of tail 34 into device1. It is intended that the 1-bit biosensor code associated with a givenbiosensor be randomly distributed, i.e., one-half of all biosensors 30are intended to have a “0” 1-bit biosensor code, and one-half of allbiosensors 30 are intended to have a “1” 1-bit biosensor code. Themanner in which this 1-bit biosensor code is used to detect biosensorreuse is discussed below in the software description.

Hardware Description

FIG. 8 is a block diagram of a preferred embodiment of the internalelectronics (hardware) of device 1. The hardware consists of twoinstrumentation amplifiers (INA) 100, 101 with differential inputscoming from the two pairs of active electrodes 41, 42 and 43, 44. In thepreferred embodiment, these INAs have a typical input impedance ≧10¹⁰(10 to the 10^(th) power) Ohms and a common mode rejection ratio 90 dB.The INAs 100, 101 share a common reference input coming from referenceelectrode 45. The outputs of INAs 100, 101 are fed into a 2×1 switch 102that determines which of the two channels will be acquired andprocessed. Switch 102 is controlled by the microcontroller 108, with thechannel selection determined by the test control software (see below).The channel selection may be different at different stages of thetesting. The output of switch 102 is input into a band-pass filter 104.In the preferred embodiment, band-pass filter 104 has a low frequencycutoff of 2 Hz and a high frequency cutoff of 4900 Hz. The output ofband-pass filter 104 is then digitized by the A/D converter 106, withthe digital output going into the microcontroller 108 for storage andprocessing.

Microcontroller 108 triggers the high voltage stimulator 116 to delivernerve stimulation to the patient via cathode 10 and anode 11. In apreferred embodiment, the high voltage stimulator 116 is a constantcurrent stimulator that generates a monophasic square DC pulse with aduration of 50 to 100 μsecs. The output voltage of the high voltagestimulator is 400-440 V, with a typical value of 420 V. The high voltagestimulator is capable of delivering up to 100 mA into a 3.3 kOhm load.

Microcontroller 108 controls the user interface components including LED24, LCD 26, and power/test button 22. Microcontroller 108 alsocommunicates with an isolated USB port 20 (FIG. 3) for externalcommunication (such as with a PC). The internal electronics of device 1are powered from a single battery 109. In the preferred embodiment, thisis the commonly-available 3V Lithium battery CR123A.

Principles of Operation

A nerve conduction test is performed on the patient by placing device 1against the patient in the manner shown in FIG. 2 and described above.When in this disposition, cathode 10 is located over the sural nerve asthe sural nerve passes behind the lateral malleoulus 6 (FIG. 2), andbiosensor 30 is located over (or in a worst case, adjacent to) the suralnerve as the sural nerve approaches the Achilles tendon, about 9 cm fromcathode 10. An important object of the present invention is that device1 automatically adapts to testing either the left leg or the right legof the patient. This “limb independence” is achieved because when device1 is placed on the patient as described above, one of the two electrodepairs 41, 42 or 43, 44 of biosensor 30 will overlie (or lie immediatelyadjacent to) the patient's sural nerve. The appropriate electrode pair(i.e., 41, 42 or 43, 44) will be the electrode pair which is closest tothe Achilles tendon because the sural nerve crosses the tendon about9-11 cm proximal to the lateral malleolus. In this configuration, thedistance from stimulating cathode 10 to the first electrode (41 or 43)within each electrode pair (41, 42 or 43, 44) is 9.22 cm, and this isthe distance used to determine the conduction velocity.

FIG. 9 shows an example of sural nerve responses acquired from the twoelectrode pairs (41, 42 and 43, 44). The right panel 80 shows thesignals 84 recorded from the electrode pair that overlies the nerve, andthe left panel 82 shows the signals 86 recorded from the electrode pairthat does not overlie the nerve. It will be appreciated that theelectrical signals 86 acquired by the “non-intersecting” electrode pairare small compared to the electrical signals acquired by the“intersecting” electrode pair. This is due to the signal-attenuatingeffects of volume conduction between the sural nerve and the“non-intersecting” electrode pair. By contrast, the signals 84 from the“intersecting” electrode pair are large due to the much smaller distancebetween the sural nerve and these electrodes.

Thus it will be seen that by providing two parallel electrode pairs 41,42 and 43, 44, device 1 can automatically adapt to testing either theleft leg or the right leg, with the appropriate electrode pair beingreadily determinable by a comparison of the magnitude of the signalsacquired by each electrode pair.

Software

Device 1 is controlled by a software-based control algorithm whichresides on microcontroller 108 (or, alternatively, on an associatedstorage unit). FIG. 12 provides an overview of various functional blocksof the control algorithm. Upon power up, the control algorithm is instate 150 and waits for an external event, which in the preferredembodiment may be any one of the following: biosensor port insertion,USB port insertion, and test button pressed.

Biosensor Port Insertion

This event is triggered by insertion of a biosensor 30 into biosensorport 16 of device 1. The primary purpose of this software module is toverify that a biosensor is not used across patients. Upon this eventtrigger, the control algorithm 152 reads the 1-bit biosensor codeassociated with the inserted biosensor and determines if this code,along with the recent history of earlier biosensor codes, is randomlydistributed (which it should be if the biosensor is not being reused,since the biosensors have a randomly distributed 1-bit biosensor code).In the preferred embodiment of the control algorithm, a history of themost recent twenty-four biosensor codes is checked for randomness usingthe Runs-Test, which is also called the Wald-Wolfowitz test. This test,shown at 154, determines if the series of 0s and 1s in the 24-bitsequence is random to a certain level of specificity. In the preferredembodiment, the target specificity is set at 99%. If any 24-bit sequenceis determined to be not random, then a warning message is displayed ondevice LCD 26, and the 24-bit sequence is reset. If a second 24-bitsequence fails the randomness test (function block 156), then device 1is locked by function block 158 and no further testing can be performeduntil device 1 is reset by the manufacturer.

USB Port Insertion

This part of the control algorithm is executed when a USB cable isinserted into USB port 20. Upon detection of this event, the controlalgorithm goes into the USB communications module which implements abasic serial communication protocol between device 1 and an externaldevice (such as a PC). This USB communications module supports severalfunctions including uploading the most recent test data and downloadinga software upgrade.

Test Button Pressed

This part of the control algorithm is executed when test button 22 (FIG.5) is pressed. Upon detection of this event (function block 160), thecontrol algorithm goes into the test control module which implements asural nerve conduction test. A sural nerve conduction test is comprisedof several sequential steps as described below.

STEP 1. Proper measurement of nerve conduction requires that the nerveis stimulated at the “maximal” level. This “maximal” level is defined asthe stimulus intensity such that further increasing of the intensity ofthe stimulus does not increase the nerve response. In the preferredembodiment (function block 162), this is accomplished by sequentiallyincreasing the stimulus intensity from 20 mA to 60 mA in 10 mA steps.Starting with 30 mA and with each succeeding stimulus intensity, thelast two nerve responses are compared with one another. If they aresimilar in amplitude and shape, as determined by their correlation toone another and to a generic sural nerve response template, then thestimulus intensity is considered to be maximal. In the preferredembodiment, the correlation is implemented as a sum of the products ofthe two response waveforms (or a response waveform and a generictemplate), normalized by the square root of the product of the energy ineach response waveform (or a response waveform and a generic template).However, if desired, similarity measures different from the correlationtechnique mentioned above may also be used. If a maximal stimulusintensity is not found, then subsequent data collection is performed at60 mA.

As described previously, a key object of the present invention is toautomatically adapt to measurements from the left or right leg. In orderto accomplish this, the sural nerve responses shown in panels 80, 82(FIG. 9) from the two electrode pairs 41, 42 and 43, 44 are comparedduring STEP 1 to determine which of the two pairs overlies the nerve andtherefore constitutes the optimal recording channel. In the preferredembodiment (function block 164), this is achieved by obtained suralresponses from both electrode pairs 41, 42 and 43, 44 under the samestimulus intensity conditions and comparing selected waveformcharacteristics—specifically, the responses are compared with respect totheir amplitude 125, estimated signal-to-noise ratio, and timing ofnegative peak 124. The electrode pair with a larger amplitude, highersignal-to-noise ratio, and earlier negative peak is selected. In thepreferred embodiment, the sural response comparison is performed at twostimulus intensity levels: 40 mA and the maximal stimulus intensitylevel. If the maximal stimulus intensity level is not found, thecomparison occurs at 60 mA. Nerve responses from the selected electrodepair (i.e., 41, 42 or 43, 44) are then used in STEP 2 (below) and STEP 3(below) for determining the sural nerve response amplitude andconduction velocity.

Additionally, the control algorithm of the preferred embodiment alsokeeps a history of the selected optimal recording channel from previoustests. More particularly, if a device is preferentially used to test oneleg more often than the other leg in a given test environment (e.g., dueto user preference, a particular test bed setup, etc.), thecorresponding pattern can be easily detected from the history ofprevious tests. The control algorithm can then utilize this informationto improve the test efficiency by starting the data acquisition at thepreferred recording channel. As an example, and referring now to FIG. 9,if a test starts at the non-optimal recording channel, waveforms 85A,85B, 85C will be collected. Since the acquired waveforms will not meetthe maximal stimulus intensity criteria, waveform 85D from the otherchannel will be acquired at 40 mA stimulus intensity. Comparison ofwaveforms 85C and 85D will lead to subsequent data acquisition from thesecond recording channel and waveforms 85E and 85F will be collected.Waveforms 85E and 85F will meet maximal stimulation criteria. Therefore,six waveforms (85A, 85B, 85C, 85D, 85E, and 85F) are needed to completeSTEP 1 as described above where the test starts on the non-optimalrecording channel. Alternatively, and as implemented in the preferredembodiment of the invention, if the control algorithm detects apreferential pattern in the previous test history, it starts the test atthe preferential recording channel. Then the waveform acquisitionsequence will be different. More particularly, it will start bycollecting waveforms 85E and 85F. Since these two waveforms 85E(acquired with 20 mA) and 85F (acquired with 30 mA) will meet themaximal stimulation criteria, the control algorithm will just need toacquire waveform 85B (stimulated with 30 mA) from the alternativerecording channel to allow for a comparison between the two recordingchannels. Therefore, only three waveforms (85E, 85F, and 85B) arerequired in order to complete STEP 1 when the control algorithm utilizesthe optimal recording channel history of previous tests and identifies apreferential recording channel.

STEP 2. Upon determination of the maximal stimulus intensity level,device 1 will repeatedly stimulate the sural nerve at the maximalstimulus intensity level and average the nerve responses into a meannerve response. In the preferred embodiment (function blocks 166, 168and 172), the number of waveforms averaged is either 4 or 8 depending onthe estimated signal-to-noise ratio of the first nerve response obtainedat the maximal stimulus intensity level. If the signal-to-noise ratio islow, then 8 responses are averaged, and if the signal-to-noise ratio ishigh, then 4 responses are averaged. During waveform averaging, device 1will exclude responses that are “outliers”. In the preferred embodimentof the present invention, outliers are determined by comparing a givenresponse to the running average of prior responses.

STEP 3. FIG. 10 shows an example of an averaged sural nerve response 120obtained by device 1. In the preferred embodiment (function block 174),device 1 determines three key waveform features: the nerve responseonset 122, the response negative peak 124, and the response positivepeak 126. These nerve response features are determined by a signalprocessing algorithm. The preferred embodiment of this signal processingalgorithm is demonstrated through an example waveform shown in FIG. 11.Waveform 120 is a result of averaging one or more sural nerve responses.A generic sural nerve response template 130 is also constructed from acollection of waveforms acquired from multiple test subjects under thesame data acquisition conditions (such as filter bandwidth and samplingfrequency). As template 130 is slid from left-to-right (denoting a shiftin time), a correlation between the shifted template 130 and theaveraged waveform 120 at different time shifts can be constructed as thecorrelation 132. In the preferred embodiment, the correlation isimplemented as a sum of the products of the averaged waveform and theshifted template, normalized by the square root of the product of theenergy in the averaged waveform 120 and the template 130. However, otherforms of correlations may also be used if desired. The algorithm firstdetermines the time 133 at which maximum correlation between theaveraged response 120 and a fixed generic sural nerve response template130 is achieved. The local maximum value of the averaged sural nerveresponse 120 closest to the correlation peak 133 is identified as thenegative peak 124 of the sural response. The positive peak 126 of thesural response is the subsequent local minimum of waveform 120 and isidentified by searching a pre-defined window that follows the negativepeak 124. Onset 122 is preferably determined by a combination of twomethods: curvature and two-line fit. The curvature method identifies themaximum curvature point of the averaged sural nerve response 120preceding the negative peak 124. The two-line fit method searches forthe best common point of two lines that approximate the baseline region127 and the initial rising edge 128 of average sural nerve waveform 120.

Of course, it should also be appreciated that other techniques wellknown in the art may be used to determine the nerve response onset 122,the response negative peak 124 and the response positive peak 126.

Once device 1 determines the nerve response onset 122, the responsenegative peak 124, and the response positive peak 126, the device usesthis information to determine (i) conduction velocity (CV), in metersper second, which is calculated as CV=(92.2/Onset), and (ii) theamplitude, in microvolts, which is calculated as the difference inamplitude between the negative peak 124 and positive peak 126. In apreferred embodiment of the present invention (function block 176), theCV is adjusted to compensate for the well known effect of temperature onconduction velocity before the CV is displayed on LCD 26 (FIG. 5). Moreparticularly, during the nerve conduction test, the skin surfacetemperature of the patient is measured by infrared thermometer 14 (FIG.3)—preferably one measurement is made with each stimulation. The overalltemperature is defined as the median of the individual temperatures. Ifthe median temperature is below 23 degrees C., then an error message isreported to the user and no nerve conduction results are displayed. Ifthe median temperature is 30 degrees C. or greater, then no temperaturecompensation is performed. For temperatures between 23 and 29.5 degreesC., the CV is corrected according to the following equation:CV_(Displayed)=CV_(Calculated) Q ₁₀ ^((ΔT/10))where Q₁₀ is a temperature coefficient and ΔT is the difference intemperature between 30 degrees C. and the median temperature. Thepreferred value for Q₁₀ is 1.5 based on published scientific studies.

Biosensor Code Incorporated into an Adapter Interposed Between the Tailof the Biosensor and the Biosensor Port of the Testing Device

If desired, the 1-bit biosensor code (which may also be referred to as a“reuse code”) may be incorporated into an adapter interposed between thetail of the biosensor and the biosensor port of the testing device,rather than being physically incorporated into the biosensor per se. Inthis form of the invention, the biosensor need not incorporate thetraces (e.g., traces 51F and 51G) which are selectively connected/notconnected so as to provide the 1-bit biosensor code used to detect reuseof the biosensor. Instead, the traces incorporating the 1-bit biosensorcode are carried by the adapter, which also has pass-through traces forelectrically connecting the working traces of the biosensor to thetesting device. This form of the invention can be advantageous where itis desired to detect biosensor reuse and a biosensor does not alreadyinclude the means to provide the 1-bit biosensor code.

Modifications

It should also be understood that many additional changes in thedetails, materials, steps and arrangements of parts, which have beenherein described and illustrated in order to explain the nature of thepresent invention, may be made by those skilled in the art while stillremaining within the principles and scope of the invention.

What is claimed is:
 1. A single, fully-integrated, hand-held device formeasuring sural nerve conduction velocity and amplitude in either leg ofa patient, the device comprising: a housing adapted to be hand-held by auser, the housing comprising a handle adapted to be gripped by a hand ofthe user so as to permit the device to be held against either leg of thepatient; a stimulation means resiliently mounted to the housing forelectrically stimulating a human sural nerve in either leg of thepatient; a biosensor releasably elastically mounted to the housing, thebiosensor comprising a plurality of electrodes physically disposedrelative to the housing so as to provide first and secondlaterally-spaced recording channels for detecting a sural nerve responseevoked by the stimulation means in either leg of the patient; anacquisition means carried by the housing and electrically connected tothe biosensor, the acquisition means configured for electricallyacquiring the sural nerve response detected by the first and secondlaterally-spaced recording channels; a channel determination means fordetermining which of the first and second laterally-spaced recordingchannels provides an optimal signal for the sural nerve response; aprocessing means carried by the housing and electrically connected tothe acquisition means and the channel determination means, theprocessing means configured for digitizing, processing and storing anacquired sural nerve response provided by the acquisition means anddetermined by the channel determination means to be the optimal signalfor the sural nerve response; a calculation means carried by the housingand electrically connected to the processing means, the calculationmeans configured for calculating the sural nerve conduction velocity andamplitude of a processed sural nerve response provided by the processingmeans; and a display means carried by the housing for displaying acalculated sural nerve conduction velocity and amplitude provided by thecalculation means; wherein the stimulation means and the biosensor areconfigured to be held against either leg of the patient, in the vicinityof the sural nerve, by the user manipulating the housing using thehandle in the same manner regardless of which leg is being tested.
 2. Adevice according to claim 1 wherein the calculation means is configuredto calculate the sural nerve conduction velocity using the onset of thesural nerve response.
 3. A device according to claim 1 wherein thecalculation means is configured to calculate the sural nerve conductionvelocity using the negative peak of the sural nerve response.
 4. Adevice according to claim 1 wherein the device is configured tocharacterize the sural nerve amplitude by the negative peak-to-positivepeak amplitude of the sural nerve response.
 5. A device according toclaim 1 wherein the device is configured to characterize the sural nerveamplitude by the onset-to-negative peak amplitude of the sural nerveresponse.
 6. A device according to claim 1 wherein the stimulation meanscomprises two conductive probes, at least one of which is resilientlymounted to the housing.
 7. A device according to claim 6 wherein atleast one of the said two conductive probes has a variable length whichautomatically adjusts to the distance between the housing and thepatient's leg when the device is held against either of the patient'slegs.
 8. A device according to claim 1 wherein said biosensor isreleasably mounted to said housing by a foam pad that automaticallyadjusts to the distance between the housing and either of the patient'slegs to create a consistent skin contact area when the device is heldagainst either of the patient's legs.
 9. A device according to claim 8wherein the foam pad comprises an adhesive for releasably mounting thebiosensor to the foam pad.
 10. A device according to claim 8 wherein thefoam pad comprises an adhesive for releasably mounting the foam pad tothe housing.
 11. A device according to claim 1 wherein said devicecomprises a determination means for determining a maximal stimulusintensity.
 12. A device according to claim 11 wherein said determinationmeans is configured to compare sural nerve responses at two stimulusintensities, wherein a second stimulus intensity is greater than a firststimulus intensity.
 13. A device according to claim 12 wherein thedifference between the two stimulus intensities compared by thedetermination means is 10 milliamps.
 14. A device according to claim 1wherein the channel determination means determines an optimal suralnerve response recording channel from the first and secondlaterally-spaced recording channels by determining which channelprovides a larger electrical signal and is therefore physically closestto the sural nerve.
 15. A device according to claim 1 wherein theprocessing means is configured to provide identification of the onset,negative peak, and positive peak of the sural nerve response.
 16. Adevice according to claim 1 wherein said device further comprises anon-contact temperature sensor mounted to the housing for measuring askin surface temperature in the vicinity of the sural nerve.
 17. Adevice according to claim 16 wherein said calculation means isconfigured to use the skin surface temperature measured by thenon-contact temperature sensor to compensate for temperature effects onthe sural nerve conduction velocity prior to the sural nerve conductionvelocity being displayed by the display means.
 18. A device according toclaim 16 wherein said calculation means is configured to use the skinsurface temperature measured by the non-contact temperature sensor tocompensate for temperature effects on the sural nerve amplitude prior tothe sural nerve amplitude being displayed by the display means.
 19. Adevice according to claim 16 wherein the calculation means is configuredto compare said skin surface temperature measured by the non-contacttemperature sensor against a predetermined minimum temperature and, ifsaid skin surface temperature is below the predetermined minimumtemperature, then an error message is displayed by the display means.20. A device according to claim 16 wherein the calculation means isconfigured to compare said skin surface temperature measured by thenon-contact temperature sensor against a predetermined maximumtemperature and, if said skin surface temperature is above thepredetermined maximum temperature, then an error message is displayed bythe display means.
 21. A device according to claim 16 wherein thecalculation means is configured to compute a variation of said skinsurface temperature during a test and to compare the computed variationagainst a predetermined maximum and, if the computed variation exceedsthe predetermined maximum, then an error message is displayed by thedisplay means.
 22. A device according to claim 1 wherein the biosensorcomprises a male member and the housing comprises a female member, suchthat when the male member is inserted into the female member, thebiosensor is electrically connected to the acquisition means.
 23. Adevice according to claim 22 wherein insertion of said male member ofsaid biosensor into said female member of said housing is electricallydetected.
 24. A device according to claim 1 wherein said biosensor iscoded with a bit pattern.
 25. A device according to claim 24 whereinsaid biosensor is coded with said bit pattern by selectively connectingor not connecting at least two conductive members carried by thebiosensor.
 26. A device according to claim 24 wherein said bit patternis a single bit.
 27. A device according to claim 24 wherein said a bitpattern is a random bit pattern.
 28. A device according to claim 1wherein the display means includes means for displaying an error messageif said sural nerve conduction velocity or amplitude cannot bedetermined by the calculation means.
 29. Apparatus for measuring suralnerve conduction velocity and amplitude, the apparatus comprising: ahousing; a stimulation means mounted to the housing for electricallystimulating a human sural nerve; a biosensor releasably mounted to thehousing, the biosensor comprising a plurality of electrodes fordetecting a sural nerve response evoked by the stimulation means; anacquisition means mounted to the housing and electrically connected tothe biosensor, the acquisition means configured for electricallyacquiring the sural nerve response detected by the biosensor; aprocessing means mounted to the housing and electrically connected tothe acquisition means, the processing means configured for digitizing,processing and storing an acquired sural nerve response provided by theacquisition means; a calculation means mounted to the housing andelectrically connected to the processing means, the calculation meansconfigured for calculating the sural nerve conduction velocity andamplitude of a processed sural nerve response provided by the processingmeans; and a display means mounted to the housing for displaying acalculated sural nerve conduction velocity and amplitude provided by thecalculation means; wherein the stimulation means and the biosensor aredesigned to be placed on a patient's anatomy, in the vicinity of the asural nerve, by manipulating the housing; and wherein a recent historyof biosensor bit patterns is detected and stored by the apparatus. 30.Apparatus according to claim 29 wherein said recent history is the 24most recent bit patterns detected by the apparatus.
 31. Apparatusaccording to claim 29 wherein the apparatus is configured to apply atest of randomness to said recent history of biosensor bit patterns. 32.Apparatus according to claim 31 wherein the apparatus is configured tocause a warning to be displayed by the display means if said test ofrandomness indicates that the recent history of bit patterns is unlikelyto be random.
 33. Apparatus according to claim 32 wherein the apparatusis configured to be rendered unusable—if said warning has been displayedby the display means and a second test of randomness on a subsequentrecent history of bit patterns indicates a lack of randomness. 34.Apparatus according to claim 33 wherein the apparatus is configured torequire a reset by the manufacturer prior to further use.
 35. Apparatusaccording to claim 31 wherein said test of randomness applied by theapparatus is the Runs-Test.
 36. A single, fully-integrated, hand-heldnerve conduction testing device for measuring sural nerve conductionvelocity and amplitude in either leg of a patient, the device comprisinga hand-held component and a single-patient use biosensor component,wherein the biosensor component is both physically and electricallyconnected to the hand-held component to acquire a sural nerve response;wherein the hand-held component comprises a housing adapted to behand-held by a user the housing comprising a handle adapted to begripped by a hand of the user so as to permit the device to be heldagainst either leg of the patient, and a stimulation means resilientlymounted to the housing for electrically stimulating a human sural nervein either leg of the patient; wherein the single-patient use biosensorcomponent comprises a biosensor unit releasable elastically mounted tothe housing, the biosensor unit comprising a plurality of electrodesphysically disposed relative to the housing so as to provide first andsecond laterally-spaced recording channels when the biosensor unit ismounted to the housing for acquiring the sural nerve response evoked bythe stimulation means in either leg of the patient; wherein thehand-held component further comprises an acquisition means carried bythe housing and electrically connected to the biosensor unit, theacquisition means configured for electrically acquiring the sural nerveresponse detected by the first and second laterally-spaced recordingchannels, a channel determination means for determining which of thefirst and second laterally-spaced recording channels provides an optimalsignal for the sural nerve response, a processing means carried by thehousing and electrically connected to the acquisition means and thechannel determination means, the processing means configured fordigitizing, processing and storing an acquired nerve response providedby the acquisition means and determined by the channel determinationmeans to be the optimal signal for the sural nerve response, acalculation means carried by the housing and electrically connected tothe processing means, the calculation means configured for calculatingthe sural nerve conduction velocity and amplitude of a processed nerveresponse provided by the processing means, and a display means carriedby the housing for displaying a calculated sural nerve conductionvelocity and amplitude provided by the calculating means; and whereinthe stimulation means and the biosensor unit are configured to be heldagainst either leg of the patient, in the vicinity of the sural nerve,by the user manipulating the housing using the handle in the same mannerregardless of which leg is being tested.
 37. A device according to claim36 wherein the stimulation means comprises: a pair of stimulatingelectrodes, at least one of the stimulating electrodes having anadjustable height, to deliver electrical current to the patient so as tostimulate the sural nerve under a varying surface anatomy.
 38. A deviceaccording to claim 36 wherein the hand-held component comprises abiosensor port to provide electrical connection to the biosensorcomponent which is physically attached to the hand-held componentthrough an adhesive-coated foam pad.
 39. A device according to claim 36wherein the stimulation means comprises a pair of stimulation probes,wherein at least one of the probes is spring-mounted so as to allow fulland complete contact between a tip of the probe and a skin surface ofuneven height of either leg of the patient.
 40. A device according toclaim 36 further comprising a temperature sensing probe mounted to thehousing so as to allow skin temperature measurements.
 41. A deviceaccording to claim 36 further comprising a pad made of a flexiblematerial positioned between the housing and the biosensor unit.
 42. Adevice according to claim 41 further comprising an adhesive coating oneach side of the pad to provide a secure but not permanent bond between(i) the pad and the housing, and (ii) the pad and the biosensor unit.43. A device according to claim 36 wherein an electrical connectionbetween the hand-held component and the biosensor component is achievedby connecting a female connector disposed on the hand-held component anda male connector disposed on the biosensor component.
 44. A deviceaccording to claim 36 wherein the biosensor unit comprises at least twopairs of active electrodes.
 45. A device according to claim 44 whereinthe at least two pairs of active electrodes are configured so that atleast one pair of active electrodes will overlay the sural nerve fordetection of the sural a nerve response evoked by the stimulation means.46. A device according to claim 36 wherein the biosensor unit comprisesa plurality of traces, at least two of which are not connected toelectrodes.
 47. Apparatus according to claim 46 wherein the traces notconnected to electrodes form various combinational patterns among themand are decoded by electronics embedded in the housing.
 48. A deviceaccording to claim 47 wherein the various combinational patterns areconfigured to provide a means for automatically recognizing at least oneof: proper connection of the biosensor component to the hand-heldcomponent; the identification of the biosensor model being connected tothe housing; or identification of the biosensor manufacturer.
 49. Adevice according to claim 36 further comprising a software controlmodule configured to automatically detect the electrical connection ofthe biosensor unit with the housing and initiate proper test setupsbased on biosensor type.
 50. A device according to claim 49 wherein saidsoftware control module is configured to recognize a predeterminedcharacteristic of the biosensor unit.
 51. A device according to claim 50wherein said software control module is configured to use thepredetermined characteristic of the biosensor unit to determine alikelihood that the biosensor unit has been re-used across multiplepatients through an analysis of a retained biosensor unit characteristichistory from each biosensor unit electrical connection.
 52. A deviceaccording to claim 36 further comprising a software control moduleconfigured to automatically determine a stimulus intensity level thatthe stimulation means must generate to evoke a maximum sural nerveresponse by analyzing the sural nerve responses acquired by theacquisition means and by controlling subsequent stimulus intensitylevels.
 53. A device according to claim 52 wherein the software controlmodule is configured to analyze waveform features of the acquired suralnerve response, where the waveform features include amplitude, negativepeak time, similarity of the sural nerve response waveform to a knowntemplate, and similarity of the sural nerve response waveform to thesural nerve response waveform acquired at lower stimulus intensity. 54.A device according to claim 36 wherein said channel determination meansis configured to select a preferred recording channel from the first andsecond laterally-spaced recording channels by analyzing a collection ofsural nerve response waveform features from the sural nerve responsedetected by the first and second laterally-spaced recording channels andacquired by the acquisition means.
 55. A device according to claim 54wherein the collection of sural nerve response waveform featuresanalyzed by the channel determination means includes amplitude,signal-to-noise ratio, negative peak time, and nerve response waveformconformity to a known template.
 56. A device according to claim 54further comprising a software control module that analyzes the frequencydistribution of the collection of sural nerve response waveform featuresdetected by the recording channel that has been selected as thepreferred recording channel in prior tests so as to determine whichelectrode recording pair associated with the preferred recording channelis more likely to overlay the sural nerve.
 57. A device according toclaim 56 wherein said software control module is configured to change adefault electrode pair.
 58. A device according to claim 36 furthercomprising a software control module configured to predict a number ofsural nerve responses needed to form an averaged nerve response byestimating a noise level based on a sural nerve response waveformsegment prior to the onset of stimulation and by estimating theamplitude of the sural nerve response evoked by maximal stimulation. 59.A device according to claim 36 further comprising a software controlmodule configured to reject outlier sural nerve response waveforms whenmultiple sural nerve response waveforms are being acquired for thepurpose of forming an averaged sural nerve response waveform.
 60. Adevice according to claim 59 wherein the device is configured toclassify an individual sural nerve response waveform as one of theoutlier sural nerve response waveforms if its correlation to a runningaverage of sural nerve response waveforms is below a threshold or if theindividual sural nerve response waveform possesses a large percentage ofextreme values based on a time-locked comparison of multiple sural nerveresponse waveforms.
 61. A device according to claim 59 wherein thesoftware control module is further configured to analyze the averagedsural nerve response waveform to identify predetermined sural nerveresponse features.
 62. A device according to claim 61 wherein thepredetermined sural nerve response features analyzed by the softwarecontrol module comprise at least one selected from the group consistingof signal onset, negative peak and positive peak.
 63. A device accordingto claim 62 wherein the predetermined sural nerve response features areused to determine the sural nerve conduction parameters of onsetconduction velocity and peak-to-peak amplitude.
 64. A device accordingto claim 36 further comprising a non-contact temperature sensor whereinthe non-contact temperature sensor continuously obtains temperaturemeasurements of the skin near the sural nerve when it is beingstimulated.
 65. A device according to claim 64 further comprising asoftware control module, wherein the software control module isconfigured to analyze the obtained temperature measurements to determinethe reliability of the temperature measurements and the appropriatenessof a test condition.
 66. A device according to claim 65 wherein saidsoftware control module is configured to calculate statistics includingstandard deviation and median value of the temperature measurements. 67.A device according to claim 66 wherein, when the standard deviationexceeds a predetermined threshold, said software control module isconfigured to discard test results.
 68. A device according to claim 66wherein, when the median temperature is below a predetermined threshold,said software control module is configured to also discard the testresults.
 69. A device according to claim 64 further comprising asoftware control module configured to automatically compensate formeasured sural nerve conduction velocity as a result of low skintemperature.
 70. A device according to claim 69 wherein the softwarecontrol module is configured to direct the calculation means tocompensate for changes in sural nerve conduction velocity due to skintemperature using a table of predetermined values.
 71. A single,fully-integrated, hand-held nerve conduction testing device formeasuring sural nerve conduction velocity and amplitude in either leg ofa patient, the device comprising a hand-held component and asingle-patient use biosensor component, wherein the biosensor componentis both physically and electrically connected to the hand-held componentto acquire a sural nerve response; wherein the hand-held componentcomprises a housing adapted to be hand-held by a user, the housingcomprising a handle adapted to be gripped by a hand of the user so as topermit the device to be held against either leg of the patient, and astimulation means resiliently mounted to the housing for electricallystimulating a human sural nerve in either leg of the patient; whereinthe single-patient use biosensor component comprises a biosensor unitreleasably elastically mounted to the housing, the biosensor unitcomprising a plurality of electrodes for detecting a sural nerveresponse evoked by the stimulation means in either leg of the patient;wherein the hand-held component further comprises an acquisition meanscarried by the housing and electrically connected to the biosensor unit,the acquisition means configured for electrically acquiring the suralnerve response detected by the biosensor unit, a processing meanscarried by the housing and electrically connected to the acquisitionmeans, the processing means configured for digitizing, processing andstoring an acquired nerve response provided by the acquisition means, acalculation means carried by the housing and electrically connected tothe processing means, the calculation means configured for calculatingthe sural nerve conduction velocity and amplitude of a processed nerveresponse provided by the processing means, and a display means carriedby the housing for displaying a calculated sural nerve conductionvelocity and amplitude provided by the calculating means; and whereinthe stimulation means and the biosensor unit are configured to be heldagainst either leg of the patient, in the vicinity of the sural nerve,by the user manipulating the housing using the handle; wherein thedevice further comprises a software control module that automaticallydetects the connection of the biosensor unit with the housing andinitiates proper test setups based on biosensor type; wherein saidsoftware control module recognizes a predetermined characteristic of thebiosensor unit; and wherein said software control module uses thepredetermined characteristic of the biosensor unit to determine thelikelihood that the biosensor unit has been re-used across multiplepatients through the analysis of a retained biosensor unitcharacteristic history from each biosensor unit connection.